Potassium Carbonate → 2-[3-(4-Methoxy-1-piperidinyl)propyl]-1H-isoindole-1,3(2H)-dione

HRID 1669215

Reaction equation

[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.Br[CH2:10][CH2:11][CH2:12][N:13]1[C:17](=[O:18])[C:16]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:15]2[C:14]1=[O:23].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][O:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:10][CH2:11][CH2:12][N:13]2[C:17](=[O:18])[C:16]3[C:15](=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:14]2=[O:23])[CH2:5][CH2:4]1

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of 4-methoxypiperidine (286) (4.1 g, 35.3 mmol), N-(3-bromopropyl)phthalimide (9.0 g, 33.6 mmol) and K2CO3 (7.0 g, 50.4 mmol) in DMF (80 mL) was stirred at 50° C. for 16 h. The solution was cooled, the solvent evaporated and the residue partitioned between water (150 mL) and EtOAc (150 mL). The organic fraction was washed with water (2×50 mL) and brine (50 mL), dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of MeOH/DCM, to give phthalimide 305 (6.0 g, 59%) as a white solid: 1H NMR δ 7.81-7.86 (m, 2H, Harom), 7.67-7.73 (m, 2H, Harom), 3.75-3.79 (t, J=7.0 Hz, 2H, CH2N), 3.28 (s, 3H, OCH3), 3.09-3.17 (m, 1H, CHO), 2.63-2.70 (m, 2H, CH2N), 2.39 (t, J=7.0 Hz, 2H, CH2N), 2.01-2.08 (m, 2H, CH2N), 1.85 (p, J=7.0 Hz, 2H, CH2), 1.74-1.81 (m, 2H, CH2), 1.37-1.46 (m, 2H, CH2). Anal. calcd for C17H22N2O3: C, 67.5; H, 7.3; N, 9.3. Found: C, 67.3; H, 7.4; N, 9.3%.

Workup

temperatureThe solution was cooled
customthe solvent evaporated
customthe residue partitioned between water (150 mL) and EtOAc (150 mL)
washThe organic fraction was washed with water (2×50 mL) and brine (50 mL)
customdried
customthe solvent evaporated
customThe residue was purified by chromatography
washeluting with a gradient (0-5%) of MeOH/DCM

Sources & evidence

ORD record: ord-9b7b960dd3fe4fb9a99f863ec5ee8752
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989451B2

Linked notes

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